Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

被引：43

作者：

Jarrad, Angie M. ^{[1
]}

Karoli, Tomislav ^{[1
]}

Debnath, Anjan ^{[2
]}

Tay, Chin Yen ^{[4
]}

Huang, Johnny X. ^{[1
]}

Kaeslin, Geraldine ^{[1
]}

Elliott, Alysha G. ^{[1
]}

Miyamoto, Yukiko ^{[3
]}

Ramu, Soumya ^{[1
]}

Kavanagh, Angela M. ^{[1
]}

Zuegg, Johannes ^{[1
]}

Eckmann, Lars ^{[3
]}

Blaskovich, Mark A. T. ^{[1
]}

Cooper, Matthew A. ^{[1
]}

机构：

[1] Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, Brisbane, Qld 4072, Australia

[2] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[4] Univ Western Australia, Marshall Ctr Infect Dis Res & Training, Perth, WA 6099, Australia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 101卷

基金：

澳大利亚国家健康与医学研究理事会; 英国惠康基金;

关键词：

Nitroimidazole; Click chemistry; Antibiotic; Anaerobe; IN-VITRO; DRUG; RESISTANCE;

D O I：

10.1016/j.ejmech.2015.06.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lambda. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G.. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. (C) 2015 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页码：96 / 102

页数：7

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